Diagnostic Criteria for MDMA abuse and dependence

September 9, 2009

A recent paper on the test / re-test reliability of diagnostic criteria for MDMA abuse and dependence is fascinating. Foremost because the nature of substance abuse is always a fun topic for discussion when you are dealing with a compound which the users argue so strenuously is perfectly benign. Even more so because the advocacy position tends to put a finer point on the argument about just how to draw lines between ordered and disordered behavior within what is very likely a continuous distribution. The paper also shows some of the limitations of trying to fit drugs which have very distinct subjective experience profiles, use patterns and even dependence modes/risks into a single (albeit reasonably flexible) diagnostic strategy.In their paper Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study, Cottler and colleagues are primarily focused on whether diagnostic criteria for MDMA abuse and dependence (there are distinct diagnoses for some substances of abuse within the Diagnostic and Statistical Manual of Mental Disorders, but not for MDMA which falls under the general abuse criteria) are reliable. As you might imagine, it is a pretty important part of medical diagnosis that a given clinical test gives the same answer when repeated for the same individual in close temporal proximity. It is no great leap of genius to see that reliability is even more important when the diagnostic instrument consists of asking people about their affect and behaviors. Particularly when the behaviors are illegal and socially stigmatized.

One of the more interesting things about 3,4-methylenedioxymethamphetamine (aka “Ecstasy”) is that it has structural, pharmacological, behavioral and human subjective properties that make it similar to both the amphetamine-class psychomotor stimulants and the classic hallucinogens (such as LSD, mescaline, psilocybin, etc). Consequently, one of the additional research goals for the present study was to further characterize the nature of MDMA abuse and dependence; such properties can be quite different between hallucinogen and stimulant drugs. This investigation can also be placed in a broader context of future revisions of the DSM, i.e., to see if MDMA should remain in the generic substance abuse category, if it should be grouped with stimulants vs. hallucinogens or whether a specific category for MDMA needs to be created. At present, MDMA use is considered under the general criteria for substance abuse and substance dependence.
The study took place in St Louis, MS and Miami, FL in the USA and Sydney in Australia, from which the investigators ended up with 593 participants who had used MDMA at least 5 times in their life and at least once in the past year. The sample had a median age of 22 with median MDMA onset at 19 years of age. The median number of lifetime MDMA pills consumed was 50 (mean 212; SD=502), virtually all individuals reported lifetime alcohol and lifetime marijuana use, 64% had used other hallucinogens, 62% other stimulants, 61% cocaine and about half reported use of sedatives, opioids and inhalants. In short, a pharmacologically promiscuous user group that is quite typical of most published reports on Ecstasy using samples.
The overall proportions at test and re-test were 59% / 57 % for dependence and 15%/18% for abuse-without-dependence. Not bad at all. The investigators also used a follow-up interview procedure to identify reasons for discrepancies. The most common were “interpretation of the question changed” (39%) and “did not understand the question” (13%) and “do not know” (12%) which, at least for the former two suggests ways to refine and/or identifies the nature of the beast**. This was the main point of the study since it was based on prior work suggesting MDMA users indeed meet abuse and dependence criteria for that drug. Nevertheless it is interesting to see what this study was able to confirm of the MDMA-dependence profile.
The most-common reported diagnostic criteria for MDMA dependence were ‘withdrawal’ (68%) and ‘continued use despite knowledge of physical or psychological problems from it’ (87%). Signs of ‘tolerance’ came in at about 50% and ‘using more than intended’ at 43%. Interestingly the ‘persistent desire /unsuccessful effort to cut down or control use’ was only reported by 17% of the sample.
To touch briefly on the issue of specificity, there was some evidence from the answers to multiple sub-questions related to withdrawal that MDMA looks very much like a stimulant on this aspect. This has some sort of interesting implications given that many users apparently seek this drug for properties other than the stimulant ones. It is not inconceivable that MDMA might cause a sort-of covert stimulant dependence with the (and I am speaking very generally here) dopamine signal being covered up by the serotonin + ? signal(s) which convey the so-called empathic and pro-social subjective properties. If MDMA dependence tends to look like oral amphetamine(s) dependence then I can see where better understanding of the profile might result in earlier detection. As I always say, the Ecstasy user population tends to be highly engaged in the science of their drug of choice and has the interest and seeming ability to adopt harm-reduction practices. Therefore educating the users has a greater potential to produce harm-reduction results all by itself. Or so I argue anyway…
The recitation of results should give you enough of a flavor of the report to return to the more general topic of what it means to be dependent on a psychoactive substance. Obviously, it can mean quite different things if out of a set of 7 core criteria you only need to endorse three to be dependent. Depending on circumstances and context, some of these criteria may have greater or lesser implications when it comes to having a drug problem. This is where we start to muddy the ability to consistently classify a behavioral disorder with the real-world implications of the behavioral disorder. Conflating substance dependence with a drug problem.
The extreme example I use is of the independently wealthy adult, with no dependents or family to speak of, who just sits around and consumes his or her readily available supply of heroin, cocaine, methamphetamine, cannabis or what have you. As much or as little as s/he wants at any given time with minimal implications for being intoxicated, in withdrawal or whatever. This person may very well meet criteria for substance dependence and likely does. Does this individual have a drug problem?
The other extreme example is of the person who uses a drug very sparingly but has children and a dependent spouse. Is perhaps living economically on the edge, in a job with minimal sick days and zero tolerance for absenteeism. This individual may have very little to report in terms of the physiological criteria that most people think of as being genuine dependence. Yet his or her single criterion of interference with ‘recreational, occupation or social activities’ may represent a huge drug problem.
I believe this is exactly the place where I get into the more fervent discussions when I assert that cannabis or MDMA cause dependence. Because many people have a hard time dissociating the concept of a drug problem from specific diagnostic criteria that they find highly salient (such as directly observable and highly dramatic somatic signs of withdrawal from opiate dependence). Difficulty considering anything that does not involve essentially daily use as a true addiction. Add to this the fact that recreational, occupational and social problems can be disguised and are highly variable in importance to different people. If recreational drug use attenuates educational and vocational attainment…is this a problem? Opinions vary.
Others insist from an individual liberties position that if someone chooses to keep using despite knowing it is degrading their health (or social or vocational pursuits for that matter), they can choose to do so and this is no sign of a problem. (Skydiving and rock climbing has a tendency to come up at this point.) I think this one misses a pretty important point about our erroneous attribution of our motivations for drug consumption. I am not certain why but people hate to consider that they are subject to behavioral conditioning. Especially when there is a psychoactive compound involved which triggers reward pathways and, ultimately, co-opts or disrupts those pathways. When someone is well along the addiction path, it is not at all clear to me that libertarian concepts of free-choice really apply. And I think it is unduly and inhumanely punitive to adopt the notion that an individual has to suffer the consequences of the presumptively “free” choices made in the initial uses of a given drug.
This paper creates the impression in this reader that MDMA dependence is characterized more by pharmacological issues of tolerance and withdrawal and less by life-interference issues. Although knowledge of MDMA-induced harm was a common criterion endorsed, the issues of interference with recreational, social or vocational pursuits were comparatively less frequent. Having difficulty cutting down use or quitting was likewise uncommon which may very well be related to the prior issue of real-life implications of MDMA dependence. Personally, I tend to think of this as less of a drug-problem when it comes to compulsive use (acute harm is a different kettle of fish) issues. For me, one of the biggest backstops on what represents a problem is a treatment seeking population who has tried (frequently repeatedly) to quit and can’t quite manage to avoid relapsing. The data in this paper do not seem to argue strongly for such a population, despite a rather impressive percentage of users that endorse the more directly pharmacologically related dependence criteria.
__
*DSM-IV-TR defines substance abuse as
A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions or expulsions from school; neglect of children or household)
2. Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
3. Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct)
4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)
B. The symptoms have never met the criteria for Substance Dependence for this class of substance.
and substance dependence (ibid) as:
…substance dependence by the American Psychiatric Association) is defined as a maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three (or more) of
the following, occurring any time in the same 12-month period:
1. Tolerance, as defined by either of the following:
(a) A need for markedly increased amounts of the substance to achieve intoxication or the desired effect
or
(b) Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
(a) The characteristic withdrawal syndrome for the substance
or
(b) The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms.
3. The substance is often taken in larger amounts or over a longer period than intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover
from its effects.
6. Important social, occupational, or recreational activities are given up or reduced because of substance use.
7. The substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused or exacerbated by the substance (for example, current cocaine use despite recognition of cocaine-induced depression or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).
**It is not shocking that being asked if you attribute certain behaviors or feelings to MDMA use or discontinuation might start a rumination process that leads you to a different answer the next time you are asked.
Citation:Cottler, L., Leung, K., & Abdallah, A. (2009). Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study Addiction, 104 (10), 1679-1690 DOI: 10.1111/j.1360-0443.2009.02649.x

From what I’ve been told by people who know, MDMA doesn’t cause any actual hallucinations
So I hear. Then again, classic hallucinogen class drugs don’t necessarily cause “hallucinations” at every dose either.
People struggle to put descriptors on the MDMA subjective experience. “empathogen” is a popular one but any way you look at it the drug probably deserves to head its own non-stimulant and non-classic-hallucinogen category…
OTOH, in animal models the drug can look very much like the stimulant that it is (structurally speaking) and somewhat like a classic hallucinogen (it has direct agonist properties at serotonin receptors in addition to the indirect serotonin-releasing/transporter blocking effects).

Everyone I’ve ever known who has tried MDMA, including myself, has gone through a brief phase of overuse, during which tolerance built extremely quick, and then stopped using it (in my case) or rarely, as in less than yearly used it.
I’m always interested to hear these studies because I wonder who these regular users are who somehow manage to take it daily and not be tolerant within days or weeks.
I also wonder how pure their dosage is, since additional substances is a huge problem with ecstasy pills. A lot of uses don’t realize that their “speedy” pills have low amounts of MDMA.

It’s very insightful that you’re picking up on the stimulant effects. Perhaps what these people are reporting is actually their response to the stimulants in the pill and not specifically the MDMA?
Is is possible to do a study on people who’ve only every been exposed to MDMA (as opposed to the ill-defined stuff called Ecstasy) and don’t have the polydrug experience all users seem to have?

I’m always interested to hear these studies because I wonder who these regular users are who somehow manage to take it daily and not be tolerant within days or weeks.
They are not taking it daily. The median stats of a three year interval from initiation to time of study (19 to 22) and the median 50 total MDMA tablets consumed (or even the mean of 212) shows this pretty clearly. The many, many other studies which report estimates of MDMA intake in their subject populations likewise fail to identify anything close to a daily intake in all but a very sharply limited number of cases.It’s very insightful that you’re picking up on the stimulant effects. Perhaps what these people are reporting is actually their response to the stimulants in the pill and not specifically the MDMA?
MDMA IS a stimulant. It is structurally similar to other amphetamine compounds, stimulates locomotor activity in some (not all) animal models and is described subjectively as similar to amphetamines in both human and animal tests that get at this question. There are also ways to identify non-stimulant characteristics. The only question is when such properties dominate and when they do not. In the present case, withdrawal symptoms were similar to those caused by the classic stimulants. There is nothing on the face of what we know from laboratory studies with MDMA only in humans and animals, frequently in dose-response designs, that makes it a crazy idea that there would be stimulant-like effects.
Now, is it possible that somehow those individuals that endorsed stimulant withdrawal characteristics also, across an extended interval of variable use, consistently got Meth-heavy tablets instead of MDMA-dominating ones? Possible. But the available tablet testing data do not support this notion- something around half of street Ecstasy tablets submitted to a harm-reduction testing service are MDMA-only for example. Similar numbers have been published from other sources (generally police seizures).Is is possible to do a study on people who’ve only every been exposed to MDMA (as opposed to the ill-defined stuff called Ecstasy) and don’t have the polydrug experience all users seem to have?
Very doubtful. And if you did round up such a population of MDMA-only users who used enough* to be likely to exhibit dependence… there would be very serious questions about how representative they could possibly be.
*I am curious about a cutoff for study entry that was as low as 5 lifetime uses which produced a median of 50 lifetime uses in the ultimate sample. If I didn’t miss something here, it suggests that once you’ve taken MDMA at least 5 times, you are generally going to take it a bunch more times. wish they’d provided the inter-quartile range, dangit!

Very interesting, thanks for the follow up.
I’m not sure why you say that the tablet testing data doesn’t support the possibility mentioned when, as you say, something like only half of them are pure. As far as I observed, people often ask for a mix of speedy or non-speedy, or for particular type on a given day, often because they were chasing a thrill that their tolerance didn’t give them with only pure tabs.
In any case, very interesting, and sorry I didn’t catch that it wasn’t daily use that was being reported on.

As far as I observed, people often ask for a mix of speedy or non-speedy, or for particular type on a given day, often because they were chasing a thrill that their tolerance didn’t give them with only pure tabs.
Fair enough. I was basically giving the null hypothesis. In my view this would be that the sample is essentially random, they mean MDMA when they attempt to procure “Ecstasy” and their access to Ecstasy is not preferential for any particular source. With respect to this latter we do not know a whole lot about marketshare issues but again, of the testing data that are out there something on the order of half of street Ecstasy tablets might be expected to contain MDMA as the only active component.
It is perfectly valid to hypothesize, as I suppose you are, that those who ended up in these samples (three cities) perhaps were intentionally seeking out Ecstasy that has a high probability of containing a lot (or all) methamphetamine, amphetamine or possibly MDA.
One wonders if it is indeed the case the users are looking for the other amphetamines, they are not better about specifying what they want, getting it and reporting it as such to, e.g., researchers? Are they just locating the pharmacological dumbass fraction, so to speak?
[ and btw, if anyone needs anything citable for this notion that users seek Ecstasy of different subjective character such as speedy-vs-dopey, try Levy et al 2005 DOI ]

Numerous MDMA users–this is back in the 1980s, when the shit was totally pure–have told me that there were no withdrawal symptoms. They have reported the opposite: an exceedingly pleasant afterglow following an episode of MDMA use that could last for many days.
Co-blogger is gonna go apeshit, but based on what I have been told by many people who have had a lot of experience with known-pure MDMA, I strongly suspect that a lot of the adverse epidemiological outcomes are due to impure shit.

excellent post, fascinating topic.
I certainly agree that there are nooks and crannies of the DSM system that aren’t as well-validated as they should be, but on the other hand I don’t necessarily support the current efforts underway in the DSM-V consortium.
One of the key elements of DSM-IV criteria for both abuse and dependence is the “maladaptive pattern.” You touch on this with your example of the rich person whose use does not interfere with functioning. In your example of “recreational drug use [that] attenuates educational and vocational attainment” I think you’re getting at the question of whether it’s a problem if the patient doesn’t care. This misses a key aspect of medical care of people with abuse and addiction problems, which is lack of awareness, and in extreme cases, active denial, of a problem. Good medical care requires a certain degree of assuming the authority to decide what’s best for the patient.
As for “educating the user” to induce harm-reduction practices, my experience (as a once-practicing neurologist who’s treated too many addicts) is that regardless of the drug, and regardless of how smart or educated the user, self-interest almost always trumps medical education. The user hears what he/she wants to hear. The MDMA crowd tends to be knowledgeable only about the benign aspects of the drug.
This is just my opinion, and does not reflect the opinion of my employer or any of my colleagues. I have no conflict-of-interest involving either DSM-V or MDMA.

Numerous MDMA users–this is back in the 1980s, when the shit was totally pure–have told me that there were no withdrawal symptoms. They have reported the opposite: an exceedingly pleasant afterglow following an episode of MDMA use that could last for many days.
That’s wonderful and all but the Tue/Wed affective disturbance after a weekend of rolling is sufficiently well described in both the harm-reduction/advocacy sites/forums and in research studies as to make your anecdotes unlikely to capture the whole story. Back in the 1980s as you put it, the use episode was proportionally speaking more likely to be the quiet whoa-dude location and less likely to be the rave…that changed dramatically through the 1990s when Ecstasy use took off…
So a lack of affective disturbance in your anecdotes may have to do with dose and context as much as it does with purity…

It sounds to me like it’s still very much an open question whether or not there can be non-addictive, non-harmful/maladaptive usage patterns.
David, certainly an addict tends to focus on the beneficial effects of their drug of choice, but can you really write off every MDMA user as impervious to harm-reduction information and still consider yourself to be giving good care?

As for “educating the user” to induce harm-reduction practices, my experience (as a once-practicing neurologist who’s treated too many addicts) is that regardless of the drug, and regardless of how smart or educated the user, self-interest almost always trumps medical education. The user hears what he/she wants to hear.
But the vast majority of MDMA users are not compulsively using “addicts” in my view. It is damn hard to identify any MDMA-using populations that use daily or even several times per week, week in / week out. Contrast this to studies which seek to identify methamphetamine users who use on such a schedule-relatively easy to locate.
Comparatively speaking the MDMA use is under some degree of control.
I’d refine your point as being that the MDMA consumer/advocate is seeking to continue using, yes, but is willing to modify their behavior if they think it makes it safer. without blowing the experience, of course.
chill-out rooms, prescriptions for water drinking, admonitions not to take too often, to watch the dose, tryptophan loading before or after, various other supplements, … all of these fall under what I am referring to. You can find them easily on advocacy websites for MDMA. In contrast I rarely see similar advice tied to something related to scientific investigation of mechanism/harm for methamphetamine, cocaine..or heck pretty much any other drug.

it’s still very much an open question whether or not there can be non-addictive, non-harmful/maladaptive usage patterns
Not really. Except for that very tiny vanishing minority of highly unique individual liabilities, people taking a given drug in a genuinely typical starter dose range just once meet your criteria.
After that all you are doing is arguing about thresholds. I think through investigations we can get closer approximations for various risk categories. And our estimates will apply to a lot of individuals, statistically speaking. But 100% guarantees for each and every specific individual? For continuing use? not going to be knowable.

DM: “I’d refine your point as being that the MDMA consumer/advocate is seeking to continue using, yes, but is willing to modify their behavior if they think it makes it safer. without blowing the experience, of course.”
I agree that the typical ecstasy user is not as tied up in their habit as many other more addictive drugs, and is perhaps more open to discussion.
Perhaps you’re looking at safety as relating to short-term effects. While not definitive, animal toxicology studies point to permanent depletion of specific fibers in the serotonin system, and human studies with PET suggest decreased limbic metabolic rates in long-term ecstasy users. see Addiction 2006 v101(3):348 for a review. My read is that either heavy or long-term use is associated with irreversible brain damage. I don’t know any way to make that “safer.”

I think you’re getting at the question of whether it’s a problem if the patient doesn’t care.
It is not so much a matter of doesn’t care, as it is; where’s the harm? and Does the individual substance user care about the harm, in comparison to the damage the use is doing to his or her body? While heavy use may cause more physical damage more quickly, they may well feel that the perceived benefit of intoxication outweighs the damage. Not much different, except in concentration, than someone who drinks moderately or who is even a moderate cocaine, methamphetamine or MDMA user. There is some damage being done in all of those cases, damage that the user believes is justified by the intoxication and the way it makes them feel.
Now this is not to say that people don’t delude themselves all the time in regards to substance abuse and addiction. I personally did it for years, before I accepted that I have very serious addiction issues and started to learn to manage them. I am now disinclined to pretend that I don’t have addiction problems, nor am I inclined to pretend that the tradeoffs I have made are entirely benign. But it took me years just to fully integrate the extent of my self deception, much less deal with it.
But lets not pretend that every person who uses intoxicants on a frequent basis is an addict. When the only real difference between an addiction and everyday, common ingrained habits is harm and the degree of harm, we have to accept that some heavy substance users aren’t going to qualify. That doesn’t mean we can’t also accept that making that distinction is going to be complicated at best…

As for “educating the user” to induce harm-reduction practices, my experience (as a once-practicing neurologist who’s treated too many addicts) is that regardless of the drug, and regardless of how smart or educated the user, self-interest almost always trumps medical education. The user hears what he/she wants to hear.
In my experience as an addict, as the friend of and sometimes lay counselor and/or harm reduction advocate to many addicts and in my research as a student going into neuropsychology and linguistics to focus on addiction, harm reduction counseling quite often does exactly what it is intended to do – reduces harm. As a tool for the achievement of abstinence, it has as much success as anything else and probably better than some. As a tool for educating substance users on safer use or safer substances to abuse and helping provide them with the tools to function in society, it beats the shit out of anything else.
Does everyone listen? No. But a lot of people do and a lot of people learn to function, learn to use when they have “earned” the right to, or when it is not going to harm those around them. Possibly they just learn to use cannabis instead, once they have weaned off the heroin. Dead in a gutter with a needle sticking out of their arm is game over – no hope for something better. Sleeping under a bridge and smoking weed, probably drinking some – at least there is hope, though unfortunately still not a lot.

I was struck by this: median number of lifetime MDMA pills consumed was 50 (mean 212; SD=502)
I know it was beyond the scope of the paper, but I would have liked to see a breakdown of the usage groups. With an n=593, to get a mean so much higher than the median, and a SD more than double the mean, there had to have been a distinct population of very high users. 297 users took between 5-50 pills, lifetime; the other half needed to average probably around 400 doses, and need to have a subgroup SD of probably ~900, according to the back of this envelope.
I wish they’d given more information, because this is suggestive that there were possibly relevant subgroups to investigate for these measures, in particular a likely almost-daily usage group versus a lower-level “social situation”-type group

I’m in total agreement with comment #9 regarding the aftereffects of the good stuff.
I also want to comment on your observation that young women on X hung around creepy old guys. As an all but official “creepy old guy”, I too wonder why beautiful young women wouldn’t want to hang around a bunch of post pubescent pimple farms with soul patches, no jobs, no experience, no sensitivity, no refinement, and gigantic but fragile egos. Maybe the young women were following a pattern of human behavior that has been bonding generational cohorts across the ages until the story of adam and eve became official civil policy as it seems to be doing now. Lockstepped age cohorts are for salmon. Our long lived and complex social instincts benefit when young men learn how to socialize sexually from older women who’ve lost their mates and young women who wish to make the best choices deserve credit for choosing older, wiser and better providers. You’ll find this is true when you grow out of your short pants. Cheers.